Closed loop neural stimulation synchronized to cardiac cycles

ABSTRACT

Various aspects of the present subject matter relate to a method. According to various method embodiments, cardiac activity is detected, and neural stimulation is synchronized with a reference event in the detected cardiac activity. Neural stimulation is titrated based on a detected response to the neural stimulation. Other aspects and embodiments are provided herein.

CLAIM OF PRIORITY

This application is a division of U.S. application Ser. No. 12/688,575,filed Jan. 15, 2010, now issued as U.S. Pat. No. 8,406,876, which isherein incorporated by reference in its entirety.

U.S. application Ser. No. 12/688,575, filed Jan. 15, 2010, published asUS 2010/0121399 on May 13, 2010, now U.S. Pat. No. 8,406,876, is acontinuation-in-part application of U.S. application Ser. No.11/459,481, filed Jul. 24, 2006, published as US 2008/0021504 on Jan.24, 2008, now U.S. Pat. No. 7,873,413, which is herein incorporated byreference in its entirety.

U.S. application Ser. No. 12/688,575, filed Jan. 15, 2010, published asUS 2010/0121399 on May 13, 2010. now U.S. Pat. No. 8,406,876, is acontinuation-in-part application of U.S. application Ser. No.12/148,843, filed Apr. 23, 2008, published as US 2008/0200959 on Aug.21, 2008, now U.S. Pat. No. 8,131,359, which is a divisional applicationof U.S. application Ser. No. 11/125,503, filed May 10, 2005, now U.S.Pat. No. 7,493,161, both of which are herein incorporated by referencein their entirety.

U.S. application Ser. No. 12/688,575, filed Jan. 15, 2010, published asUS 2010/0121399 on May 13, 2010, now U.S. Pat. No. 8,406,876, is acontinuation-in-part application of U.S. application Ser. No.11/137,038, filed May 25, 2005, published as US 2006/0271118 on Nov. 30,2006, now issued as U.S. Pat. No. 8,473,049, which is hereinincorporated by reference in its entirety.

U.S. application Ser. No. 12/688,575, filed Jan. 15, 2010, published asUS 2010/0121399 on May 13, 2010, now U.S. Pat. No. 8,406,876, is acontinuation-in-part application of U.S. application Ser. No.12/469,012, filed May 20, 2009, published as US 2009/0228060 on Sep. 10,2009, now issued as U.S. Pat. No. 8,452,398, which is a divisionalapplication of U.S. application Ser. No. 11/099,141, filed Apr. 5, 2005,now U.S. Pat. No. 7,542,800, both of which are herein incorporated byreference in their entirety.

FIELD

This application relates generally to medical devices and, moreparticularly, to systems, devices and methods for providing neuralstimulation.

BACKGROUND

The heart is the center of a person's circulatory system. The leftportions of the heart draw oxygenated blood from the lungs and pump itto the organs of the body to provide the organs with their metabolicneeds for oxygen. The right portions of the heart draw deoxygenatedblood from the body organs and pump it to the lungs where the blood getsoxygenated. These pumping functions are accomplished by cycliccontractions of the myocardium (heart muscles). Each cycle, known as thecardiac cycle, includes systole and diastole. During systole, the heartejects blood. During diastole, the heart is filled with blood for thenext ejection (systolic) phase, and the myocardial tissue is perfused.In a normal heart, the sinoatrial node generates electrical impulsescalled action potentials. The electrical impulses propagate through anelectrical conduction system to various regions of the heart to excitethe myocardial tissue of these regions. Coordinated delays in thepropagations of the action potentials in a normal electrical conductionsystem cause the various portions of the heart to contract in synchronyto result in efficient pumping functions indicated by a normalhemodynamic performance. A blocked or otherwise abnormal electricalconduction and/or deteriorated myocardial tissue result in systolicdysfunction—because the myocytes do not contract in unison—and diastolicdysfunction—because the myocytes do not relax in unison. Decreasedsystolic and diastolic performance each contribute to a poor overallhemodynamic performance, including a diminished blood supply to theheart and the rest of the body.

The hemodynamic performance is modulated by neural signals in portionsof the autonomic nervous system. For example, the myocardium isinnervated with sympathetic and parasympathetic nerves. Activities inthese nerves modulate the heart rate and contractility (strength of themyocardial contractions). Stimulation applied to the sympathetic nervesis known to increase the heart rate and the contractility, shorteningthe systolic phase of a cardiac cycle, and lengthening the diastolicphase of the cardiac cycle. Stimulation applied to the parasympatheticnerves is known to have essentially the opposite effects.

It has been proposed to stimulate the autonomic nerves to treat abnormalcardiac conditions, such as to control myocardial remodeling and toprevent arrhythmias following myocardial infarction. During heartfailure, reduced autonomic balance (increase in sympathetic and decreasein parasympathetic cardiac tone) has been shown to be associated withleft ventricular dysfunction and increased mortality. Data furtherindicate that increasing parasympathetic tone and reducing sympathetictone may beneficially protect the myocardium from further remodeling andpredisposition to fatal arrhythmias following myocardial infarction. Itis observed that the effects of autonomic stimulation are dependent ontiming of the delivery of electrical stimuli in relation to the cardiaccycle.

SUMMARY

Various aspects of the present subject matter relate to a system.Various system embodiments comprise a reference event detection circuit,a feedback detection circuit, a stimulation control circuit, and astimulation output circuit. The reference event detection circuit isadapted to receive an input from a reference signal sensor and generatea synchronization control signal using a detected cardiac activityevent. The feedback detection circuit is adapted to receive an inputfrom a feedback sensor and generate a feedback control signal. Thestimulation control circuit is adapted to generate a stimulation controlsignal. The stimulation control circuit includes a synchronizationcircuit responsive to the synchronization control signal to time thestimulation control signal, and a therapy titration circuit responsiveto the feedback control signal to adjust the stimulation control signal.The stimulation output circuit is responsive to the stimulation controlsignal from the stimulation control circuit and is adapted to generate aneural stimulation signal for use in stimulating at least one autonomicneural target. The neural target(s) can include one, two or more neuraltargets to produce a desired response such as a desired change in heartrate, PR interval and the like.

Various system embodiments comprise a heart rate detector, a feedbackdetection circuit, a stimulation control circuit, and a stimulationoutput circuit. The heart rate detector is adapted to generate asynchronization control signal using a detected heart rate. The feedbackdetection circuit is adapted to receive an input from a cardiac datasensor and generate a feedback control signal using detected cardiacdata. The stimulation control circuit is adapted to generate astimulation control signal, and includes a synchronization circuitresponsive to the synchronization control signal to time the stimulationcontrol signal and a therapy titration circuit responsive to thefeedback control signal to adjust the stimulation control signal. Thestimulation output circuit is responsive to the stimulation controlsignal from the stimulation control circuit and is adapted to generate aneural stimulation signal for use in stimulating an autonomic neuraltarget.

Various aspects of the present subject matter relate to a method.According to various method embodiments, cardiac activity is detected,and neural stimulation is synchronized with a reference event in thedetected cardiac activity. Neural stimulation is titrated based on adetected response to the neural stimulation.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects will be apparent to persons skilled in the art upon reading andunderstanding the following detailed description and viewing thedrawings that form a part thereof, each of which are not to be taken ina limiting sense. The scope of the present invention is defined by theappended claims and their equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a neural stimulation method, according variousembodiments.

FIG. 2 illustrates a neural stimulation titration method to maintainheart rate, according to various embodiments.

FIG. 3 illustrates a neural stimulation titration method to change aheart rate, according to various embodiments.

FIG. 4 is an illustration of an embodiment of a neural stimulationsystem and portions of an environment in which system is used.

FIG. 5 is a block diagram illustrating an embodiment of a circuit of aneural stimulation system.

FIG. 6 illustrates an embodiment of a therapy titration module such asis illustrated in FIG. 5.

FIG. 7 is a block diagram illustrating an embodiment of a circuit of aneural stimulation system.

FIG. 8 is a block diagram illustrating an embodiment of a neuralstimulation system, which uses a wireless ECG to synchronize neuralstimulation to cardiac cycles.

FIG. 9 is an illustration of an embodiment of an electrode system forsensing one or more subcutaneous ECG signals.

FIG. 10 is a block diagram illustrating an embodiment of a neuralstimulation system which uses heart sounds to synchronize neuralstimulation to cardiac cycles.

FIG. 11 is a block diagram illustrating an embodiment of a neuralstimulation system which uses a hemodynamic signal to synchronize neuralstimulation to cardiac cycles.

FIG. 12 illustrates an implantable medical device (IMD), according tovarious embodiments of the present subject matter.

FIG. 13 shows a system diagram of an embodiment of amicroprocessor-based implantable device, according to variousembodiments.

FIG. 14 illustrates a system including an implantable medical device(IMD) and an external system or device, according to various embodimentsof the present subject matter.

FIG. 15 illustrates a system including an external device, animplantable neural stimulator (NS) device and an implantable cardiacrhythm management (CRM) device, according to various embodiments of thepresent subject matter.

FIG. 16 is a block diagram illustrating an embodiment of an externalsystem.

FIG. 17 illustrates a system embodiment in which an IMD is placedsubcutaneously or submuscularly in a patient's chest with lead(s)positioned to stimulate a vagus nerve.

FIG. 18 illustrates a system embodiment that includes an implantablemedical device (IMD) with satellite electrode(s) positioned to stimulateat least one neural target.

DETAILED DESCRIPTION

The following detailed description of the present subject matter refersto the accompanying drawings which show, by way of illustration,specific aspects and embodiments in which the present subject matter maybe practiced. These embodiments are described in sufficient detail toenable those skilled in the art to practice the present subject matter.Other embodiments may be utilized and structural, logical, andelectrical changes may be made without departing from the scope of thepresent subject matter. References to “an”, “one”, or “various”embodiments in this disclosure are not necessarily to the sameembodiment, and such references contemplate more than one embodiment.The following detailed description is, therefore, not to be taken in alimiting sense, and the scope is defined only by the appended claims,along with the full scope of legal equivalents to which such claims areentitled.

The present subject matter may be used in any cardiac device which hasneural stimulation capabilities, or in any neural stimulation device forcardiac applications. Various embodiments include an implantable device,and various embodiments includes an external device. The therapy may beof significant benefit in post myocardial infarction (post MI) and heartfailure (HF) patients, or in patients with other cardiovascularconditions (e.g. hypertension, syncope, etc.).

Embodiments of the present subject matter synchronize neural stimulationto the cardiac cycle (such as is disclosed in U.S. application Ser. No.11/099,141, entitled “Method and Apparatus For Synchronizing NeuralStimulation to Cardiac Cycles,” filed Apr. 5, 2005, now U.S. Pat. No.7,542,800, and incorporated by reference in its entirety) and furtherprovide stimulation feedback using a physiologic response to the neuralstimulation (e.g. a cardiac response such as a detected heart rate or anon-cardiac response such as respiration). For example, while thenervous system is stimulated to evoke a sympathetic response(sympathetic stimulation and/or parasympathetic inhibition) to increasethe heart rate, a system embodiment triggers the pulses based on ECGalignment and also monitors the change in heart rate. If the heart rateresponse is not as expected or desired, a new stimulation waveform, siteand/or vector is chosen until the appropriate increased heart rate isachieved. Likewise, a similar method can be applied to neuralstimulation to evoke a parasympathetic response (parasympatheticstimulation and/or sympathetic inhibition) to decrease the heart rate.

Closed loop systems allow chronic changes in the response to neuralstimulation to be mitigated, allow the response (e.g. rate of change) tobe controlled by observing and selecting different stimulationwaveforms, sites, and vectors for different desired rates, provide fullyautomatic neural stimulation device free from physician intervention ifdisease or other chronic affects change the neural response, and allowthe device therapy response to be tailored or a specific patient and/orimplant.

Some embodiments include a device capable of stimulating neural targetsand monitoring ECG signals that is programmed to titrate therapy basedon heart rate (steady heart rate or a heart rate increase or decreasebased on a percentage value or beats per minute or other means forquantifying the increase or decrease). Other metrics from the ECG (AVdelay, T-wave velocity, etc.) can be used to provide cardiac activityfeedback. According to various embodiments, titrating the therapyintensity includes changing a signal feature (e.g. amplitude, pulseduration, frequency, and/or waveform), neural target site (via multipleelectrodes), and/or vector (via the same or different vectors). Variousembodiments perform an iterative process where a stimulation is changedand the resulting cardiac activity is monitored. If appropriate after adesignated time course or predetermined event (e.g. the therapy is notproviding the desired cardiac activity response) the device will precedeto the next permutation of therapy.

FIG. 1 illustrates a neural stimulation method, according variousembodiments. Raw cardiac data is collected at 101. In variousembodiments, the cardiac data includes non-intracardiac data, such asmay be collected by an ECG signal or a P-wave or R wave detector, forexample. In various embodiments, the cardiac data includes sensedelectrical activity by cardiac leads. The raw data can be averaged orotherwise processed at 102. At 103, it is determined whether cardiacactivity has occurred. The detected cardiac activity triggers (with orwithout a delay) neural stimulation at 104 such that the neuralstimulation is synchronized to the cardiac activity. At 105, it isdetermined whether the resulting cardiac activity or non-cardiac effectsare desired. If the resulting cardiac activity or non-cardiac effectsare not expected, the process proceeds to 106 to change or titrate theneural stimulation therapy. Various embodiments titrate therapy byincreasing the intensity of the therapy or decreasing the intensity oftherapy. Various embodiments titrate therapy by changing a feature ofthe neural stimulation signal (e.g. amplitude, frequency, pulse durationand/or waveform). Various embodiments titrate therapy by changing astimulation vector which changes the neural stimulation. Someembodiments change the vector to change between stimulating neuraltraffic and inhibiting neural traffic. Various embodiments titratetherapy by changing the electrodes used to provide the electricaltherapy. Thus, given N electrodes, the therapy can change from using afirst set of electrodes selected from the N electrodes to a second setof electrodes selected from the N electrodes. An electrode can be in oneset but not the other, or can be in both sets. Some sets only includeelectrodes that are not in the other set.

FIG. 2 illustrates a neural stimulation titration method to maintainheart rate, according to various embodiments. Other physiologicresponses can be used in place of or in addition to heart rate. Theillustrated process generally corresponds to determining if theresulting cardiac activity or non-cardiac effects are desired andtitrating the neural stimulation accordingly, as illustrated in FIG. 1.At 205, it is determined whether the desired heart rate (e.g. range ofacceptable heart rates) has been maintained. If the heart rate has notbeen maintained, the process proceeds to 206 to change or titrate theneural stimulation therapy to maintain the heart rate.

FIG. 3 illustrates a neural stimulation titration method to change aheart rate, according to various embodiments. Other physiologicresponses can be used in place of or in addition to heart rate. Theillustrated process generally corresponds to determining if theresulting cardiac activity or non-cardiac effects are desired andtitrating the neural stimulation accordingly, as illustrated in FIG. 1.At 305, it is determined whether the heart rate is to be changed (e.g.percentage or change in beats per minute). If the heart rate is to bechanged, the process proceeds to 306 to change or titrate the neuralstimulation therapy to change the heart rate as desired.

Various neural stimulation system embodiments include an implantableneural stimulator that senses a reference signal indicative of cardiaccycles each including a predetermined type timing reference event usingan implantable reference event sensor. Various embodiments use anintracardiac lead to detect the reference event. In an embodiment, theimplantable reference event sensor is an extracardiac and extravascularsensor, i.e., a sensor that is placed external to a patient'scirculatory system including the heart and blood vessels. The deliveryof the neural stimulation pulses are synchronized to the timingreference event. Examples of the reference signal include a wirelessECG, an acoustic signal indicative of heart sounds, and a hemodynamicsignal. For example, the reference event can be a directly detectedP-wave or a P-wave derived using a detected QRS signal, signal averagingDoppler flow, and acoustic signals.

In this document, “ECG” includes surface ECG, wireless ECG andsubcutaneous ECG. In this document, “Surface ECG” refers to a cardiacelectrical signal sensed with electrodes attached onto the exteriorsurface of the skin. “Wireless ECG” refers to a signal approximating thesurface ECG, acquired without using surface (non-implantable, skincontact) electrodes. “Subcutaneous ECG” is a form of wireless ECG andincludes a cardiac electrical signal sensed through electrodes implantedin subcutaneous tissue, such as through electrodes incorporated onto animplantable medical device that is subcutaneously implanted. Asreflected in their corresponding morphologies, the surface ECG resultsfrom electrical activities of the entire heart. The wireless ECG,including but not being limited to the subcutaneous ECG, has amorphology that approximates that of the surface ECG and reflectselectrical activities of a substantial portion of the heart, up to theentire heart.

In this document, an “acoustic signal” includes any signal indicative ofheart sounds. “Heart sounds” include audible mechanical vibrationscaused by cardiac activity that can be sensed with a microphone andaudible and inaudible mechanical vibrations caused by cardiac activitythat can be sensed with an accelerometer. Known type heart soundsinclude the “first heart sound” or S1, the “second heart sound” or S2,the “third heart sound” or S3, the “fourth heart sound” or S4, and theirvarious sub-components. S1 is known to be indicative of, among otherthings, mitral valve closure, tricuspid valve closure, and aortic valveopening. S2 is known to be indicative of, among other things, aorticvalve closure and pulmonary valve closure. S3 is known to be aventricular diastolic filling sound often indicative of certainpathological conditions including heart failure. S4 is known to be aventricular diastolic filling sound resulted from atrial contraction andis usually indicative of pathological conditions. The term “heart sound”hereinafter refers to any heart sound (e.g., S1) and any componentsthereof (e.g., M1 component of S1, indicative of Mitral valve closure).

In this document, a “hemodynamic signal” includes a signal providing formonitoring, calculation, or estimation of one or more measures ofhemodynamic performance such as blood pressure or pressure-relatedparameters, cardiac output, stroke volume, volume of blood flow, changein (e.g., derivative of) the volume of blood flow, and/or velocity ofblood flow.

Various embodiments titrate therapy based on a change in heart rate,such as a percentage change or a quantitative change such as beats perminute, or based on other measurable cardiac effects. Examples ofECG-derived parameters include heart rate variability (HRV), heart rateturbulence (HRT), AV delay, and T-wave velocity. Heart sound waveformsmay be used, as well as changes in photoplethysmography, and non-cardiaceffects such as respiration and blood pressure. The therapy is titratedby means for a changeable stimulation methodology via waveformmodulation, site or vector changes.

FIG. 4 is an illustration of an embodiment of a neural stimulationsystem 407 and portions of an environment in which system 407 is used.System 407 includes implantable medical device 408 that delivers neuralstimulation pulses through leads 409 and 410, an external system 411,and a telemetry link 412 providing for communication between implantablemedical device 408 and external system 411. For illustrative purposeonly, FIG. 4 shows that lead 409 includes an electrode 413 coupled to anerve 414 of the sympathetic nervous system, and lead 410 includes anelectrode 415 coupled a nerve 416 of the parasympathetic nervous system.Neural targets can be stimulated using nerve cuffs, intravascularly-fedelectrodes positioned to transvascularly stimulate the neural targets,and stimulation electrodes wirelessly connected to the system. Neuraltargets may also be stimulated using non-electrical energy, such as maybe produced by transducers that provide ultrasonic, light and magneticenergy. Nerves 414 and 416 innervate a heart 417. In variousembodiments, implantable medical device 408 provides neural stimulationto any one or more nerves through one or more leads for modulating oneor more functions of the circulatory system including heart 417. Suchleads include implantable neural leads each including at least oneelectrode for sensing neural activities and/or delivering neuralstimulation pulses. One example of such an electrode includes a cuffelectrode for placement around an aortic, carotid, or vagus nerve. Anembodiment includes an intravascularly-placed electrode positioned in aninternal jugular vein (IJV) to stimulate a vagus nerve, or in an aortaor pulmonary artery positioned to stimulate neural targets proximatethereto.

Implantable medical device 408 delivers the neural stimulation pulsesand includes a neural stimulation circuit 418. The illustrated neuralstimulation circuit 418 includes a cardiac cycle synchronization circuit419, a therapy titration circuit 420 which receives resulting cardiacactivity feedback which can be representative of the efficacy of thetherapy. Neural stimulation circuit 418 detects a predetermined typetiming reference event from a cardiac cycle and synchronizes thedelivery of neural stimulation pulses to that timing reference event. Inone embodiment, neural stimulation circuit 418 starts a predeterminedoffset time interval upon detection of the timing reference event anddelivers a burst of neural stimulation pulses when the offset timeinterval expires. In one embodiment, implantable medical device 408 iscapable of monitoring physiologic signals and/or delivering therapies inaddition to the neural stimulation. Examples of such additionaltherapies include cardiac pacing therapy, cardioversion/defibrillationtherapy, cardiac resynchronization therapy, cardiac remodeling controltherapy, drug therapy, cell therapy, and gene therapy. In variousembodiments, implantable medical device 408 delivers the neuralstimulation in coordination with one or more such additional therapies.

External system 411 provides for control of and communication withimplantable medical device 408 by a physician or other caregiver. In oneembodiment, external system 411 includes a programmer. In anotherembodiment, external system 411 is a patient management system includingan external device communicating with implantable medical device 408 viatelemetry link 412, a remote device in a relatively distant location,and a telecommunication network linking the external device and theremote device. The patient management system allows access toimplantable medical device 408 from a remote location, for purposes suchas monitoring patient status and adjusting therapies. In one embodiment,telemetry link 412 is an inductive telemetry link. In an embodiment,telemetry link 412 is a far-field radio-frequency (RF) telemetry link.Telemetry link 412 provides for data transmission from implantablemedical device 408 to external system 411. This includes, for example,transmitting real-time physiological data acquired by implantablemedical device 408, extracting physiological data acquired by and storedin implantable medical device 408, extracting patient history data suchas occurrences of arrhythmias and therapy deliveries recorded inimplantable medical device 408, and/or extracting data indicating anoperational status of implantable medical device 408 (e.g., batterystatus and lead impedance). Telemetry link 412 also provides for datatransmission from external system 411 to implantable medical device 408.This includes, for example, programming implantable medical device 408to acquire physiological data, programming implantable medical device408 to perform at least one self-diagnostic test (such as for a deviceoperational status), and/or programming implantable medical device 408to deliver one or more therapies and/or to adjust the delivery of one ormore therapies.

FIG. 5 is a block diagram illustrating an embodiment of a circuit of aneural stimulation system 521. System 521 includes a reference signalsensor 522, a data sensor 523A adapted to sense a physiologic responseto the neural stimulation, a stimulation electrode/transducer 524, and aneural stimulation circuit 518. Reference signal sensor 522 senses areference signal indicative of cardiac cycles each including apredetermined type timing reference event. In one embodiment, referencesignal sensor 522 is an implantable reference signal sensor. The timingreference event is a recurring feature of the cardiac cycle that ischosen to be a timing reference to which the neural stimulation issynchronized. In an embodiment, reference signal sensor 522 includes anelectrode in or near the heart, such as may be incorporated in anintracardiac lead. In one embodiment, reference signal sensor 522 isconfigured for extracardiac and extravascular placement, i.e., placementexternal to the heart and blood vessels. Examples of reference signalsensor 522 include a set of electrodes for sensing a subcutaneous ECGsignal, an acoustic sensor for sensing an acoustic signal indicative ofheart sounds, and a hemodynamic sensor for sensing a hemodynamic signalindicative of hemodynamic performance. In one embodiment, an implantablemedical device has an implantable housing that contains both a referencesignal sensor 522 and neural stimulation circuit 518. In an embodiment,reference signal sensor 522 is incorporated onto the housing of animplantable medical device. In another embodiment, reference signalsensor 522 is electrically connected to an implantable medical devicethrough one or more leads. In another embodiment, reference signalsensor 522 is communicatively coupled to an implantable medical devicevia an intra-body telemetry link.

Neural stimulation circuit 518 includes a stimulation output circuit525, a reference event detection circuit 526, a feedback detectioncircuit 527, and a stimulation control circuit 528. Reference eventdetection circuit 526 receives the reference signal from referencesignal sensor 522 and detects the timing reference event from thereference signal. Stimulation control circuit 528 controls the deliveryof the neural stimulation pulses and includes a synchronization circuitor module 529 and a therapy titration adjustment circuit or module 530.Synchronization module 529 receives a signal indicative of the detectionof each timing reference event and synchronizes the delivery of theneural stimulation pulses to the detected timing reference event.Stimulation output circuit 525 delivers neural stimulation pulses uponreceiving a pulse delivery signal from stimulation control circuit 528.Data sensor 523A provides signals indicative of a physiological responseto the applied neural stimulation. A feedback detection circuit 527receives the signal indicative of the response and processes the signalto provide a neural stimulation feedback signal. In various embodiments,the response includes a cardiac activity such as heart rate, HRV, HRT,PR interval, T-wave velocity, or action potential duration. In variousembodiments the response includes a non-cardiac response such asrespiration or blood pressure. In various embodiments, the responseincludes a QT interval or atrial/ventricular refractory periods. Thetherapy titration/adjustment module 530 uses the feedback signal tomodulate or titrate the therapy generated by the stimulation outputcircuit 525 to provide the desired physiologic response (e.g. cardiacresponse or non-cardiac response). Contextual sensor(s) or input(s) 523Bare also illustrated connected to the feedback detection circuit 527 toprovide a more complete picture of a patient's physiology. The feedbackdetection circuit can provide the neural stimulation feedback signalbased on the sensor 523A and the contextual input(s) 523B. Thecontextual input(s) can be used to avoid incomplete data from affectingthe neural stimulation. Examples of contextual inputs include anactivity sensor, a posture sensor and a timer. Any one or combination oftwo or more contextual inputs can be used by the feedback detectioncircuit. For example, an elevated heart rate may be representative ofexercise rather than a reason for titrating the neural stimulationtherapy.

FIG. 6 illustrates an embodiment of a therapy titration module 630 suchas is illustrated at 530 in FIG. 5. According to various embodiments,the stimulation control circuit is adapted to set or adjust any one orany combination of stimulation features 631. Examples of stimulationfeatures include the amplitude, frequency, polarity and wave morphologyof the stimulation signal. Examples of wave morphology include a squarewave, triangle wave, sinusoidal wave, and waves with desired harmoniccomponents to mimic white noise such as is indicative ofnaturally-occurring baroreflex stimulation. Some embodiments of thestimulation output circuit are adapted to generate a stimulation signalwith a predetermined amplitude, morphology, pulse width and polarity,and are further adapted to respond to a control signal from thecontroller to modify at least one of the amplitude, wave morphology,pulse width and polarity. Some embodiments of the neural stimulationcircuitry are adapted to generate a stimulation signal with apredetermined frequency, and are further adapted to respond to a controlsignal from the controller to modify the frequency of the stimulationsignal.

The therapy titration module 630 can be programmed to change stimulationsites 632, such as changing the stimulation electrodes used for a neuraltarget or changing the neural targets for the neural stimulation. Forexample, different electrodes of a multi-electrode cuff can be used tostimulate a neural target. Examples of neural targets include the rightand left vagus nerves, cardiac branches of the vagus nerve, cardiac fatspads, baroreceptors, the carotid sinus, the carotid sinus nerve, and theaortic nerve. Autonomic neural targets can include afferent pathways andefferent pathways and can include sympathetic and parasympatheticnerves. The stimulation can include stimulation to stimulate neuraltraffic or stimulation to inhibit neural traffic. Thus, stimulation toevoke a sympathetic response can involve sympathetic stimulation and/orparasympathetic inhibition; and stimulation to evoke a parasympatheticresponse can involve parasympathetic stimulation and/or sympatheticinhibition.

The therapy titration module 630 can be programmed to change stimulationvectors 633. Vectors can include stimulation vectors between electrodes,or stimulation vectors for transducers. For example, the stimulationvector between two electrodes can be reversed. One potential applicationfor reversing stimulation vectors includes changing from stimulatingneural activity at the neural target to inhibiting neural activity atthe neural target. More complicated combinations of electrodes can beused to provide more potential stimulation vectors between or amongelectrodes. One potential stimulation vector application involvesselective neural stimulation (e.g. selective stimulation of the vagusnerve) or changing between a selective stimulation and a more generalstimulation of a nerve trunk.

The therapy titration module 630 can be programmed to control the neuralstimulation according to stimulation instructions, such as a stimulationroutine or schedule 634, stored in memory. Neural stimulation can bedelivered in a stimulation burst, which is a train of stimulation pulsesat a predetermined frequency. Stimulation bursts can be characterized byburst durations and burst intervals. A burst duration is the length oftime that a burst lasts. A burst interval can be identified by the timebetween the start of successive bursts. A programmed pattern of burstscan include any combination of burst durations and burst intervals. Asimple burst pattern with one burst duration and burst interval cancontinue periodically for a programmed period or can follow a morecomplicated schedule. The programmed pattern of bursts can be morecomplicated, composed of multiple burst durations and burst intervalsequences. The programmed pattern of bursts can be characterized by aduty cycle, which refers to a repeating cycle of neural stimulation ONfor a fixed time and neural stimulation OFF for a fixed time. Duty cycleis specified by the ON time and the cycle time, and thus can have unitsof ON time/cycle time. According to some embodiments, the controlcircuit 528 controls the neural stimulation generated by the stimulationcircuitry by initiating each pulse of the stimulation signal. In someembodiments, the stimulation control circuit initiates a stimulationsignal pulse train, where the stimulation signal responds to a commandfrom the controller circuitry by generating a train of pulses at apredetermined frequency and burst duration. The predetermined frequencyand burst duration of the pulse train can be programmable. The patternof pulses in the pulse train can be a simple burst pattern with oneburst duration and burst interval or can follow a more complicated burstpattern with multiple burst durations and burst intervals. In someembodiments, the stimulation control circuit controls the stimulationoutput circuit to initiate a neural stimulation session and to terminatethe neural stimulation session. The burst duration of the neuralstimulation session under the control of the control circuit 528 can beprogrammable. The controller may also terminate a neural stimulationsession in response to an interrupt signal, such as may be generated byone or more sensed parameters or any other condition where it isdetermined to be desirable to stop neural stimulation.

The illustrated device includes a programmed therapy schedule or routinestored in memory and further includes a clock or timer which can be usedto execute the programmable stimulation schedule. For example, aphysician can program a daily/weekly schedule of therapy based on thetime of day. A stimulation session can begin at a first programmed time,and can end at a second programmed time. Various embodiments initiateand/or terminate a stimulation session based on a signal triggered by auser. Various embodiments use sensed data to enable and/or disable astimulation session.

According to various embodiments, the stimulation schedule refers to thetime intervals or period when the neural stimulation therapy isdelivered. A schedule can be defined by a start time and an end time, ora start time and a duration. Various schedules deliver therapyperiodically. By way of example and not limitation, a device can beprogrammed with a therapy schedule to deliver therapy from midnight to 2AM every day, or to deliver therapy for one hour every six hours, or todeliver therapy for two hours per day, or according to a morecomplicated timetable. Various device embodiments apply the therapyaccording to the programmed schedule contingent on enabling conditions,such as sensed exercise periods, patient rest or sleep, low heart ratelevels, and the like. For example, the stimulation can be synchronizedto the cardiac cycle based on detected events that enable thestimulation. The therapy schedule can also specify how the stimulationis delivered.

FIG. 7 is a block diagram illustrating an embodiment of a circuit of aneural stimulation system 721. The illustrated system 721 includesreference signal sensor 722, a physiologic response data sensor 723A, astimulation electrode/transducer 724, and a neural stimulation circuit718. Neural stimulation circuit 718 includes stimulation output circuit725, a reference event detection circuit 726, a feedback detectioncircuit 727, and a stimulation control circuit 728.

Reference event detection circuit 726 includes a signal processor 735and an event detector 736. Signal processor 735 receives the referencesignal sensed by reference signal sensor 722 and processes the referencesignal in preparation for the detection of the timing reference eventsby event detector 736. Event detector 736 includes a comparator havingan input to receive the processed reference signal, another input toreceive a detection threshold, and an output producing a detectionsignal indicating a detection of the timing reference signal. In oneembodiment, signal processor 735 processes the reference signal toextract the timing reference event based on a single cardiac cycle. Inone embodiment, signal processor 735 includes a filter having apass-band corresponding to a frequency range of the timing referenceevent to prevent unwanted activities in the reference signal from beingdetected by event detector 736. In an embodiment, signal processor 735includes a blanking period generator to generate a blanking period thatblanks the unwanted activities in the reference signal. This approach isapplied when an approximate timing relationship between the timingreference event and the unwanted activities, or an approximate timingrelationship between another detectable event and the unwantedactivities, is predictable. In an embodiment, the blanking periodgenerator generates a blanking period that blanks cardiac pacingartifacts in the reference signal, i.e., unwanted activities caused bydelivery of cardiac pacing pulses. In an embodiment, signal processor735 includes a timing interval generator to generate a timing intervalbetween an intermediate event and the timing reference event. Thisapproach is applied when the intermediate event is more easilydetectable than the timing reference event and when an approximatetiming relationship between the intermediate event and the timingreference event is predictable. In an embodiment, signal processor 735processes the reference signal to provide for extraction of the timingreference event based on a plurality of cardiac cycles. In oneembodiment, signal processor 735 includes a signal averaging circuitthat averages the reference signal over a predetermined number ofcardiac cycles before the detection of the timing reference event byevent detector 736.

Stimulation control circuit 728 includes a synchronization circuit 729,a therapy titration circuit 730, an offset interval generator 737, and apulse delivery controller 738. Synchronization circuit 729 includes oneor both of a continuous synchronization module 739 and a periodicsynchronization module 740. Continuous synchronization modulesynchronizes the delivery of the neural stimulation pulses to the timingreference event of consecutive cardiac cycles. Periodic synchronizationmodule synchronizes the delivery of the neural stimulation pulses to thetiming reference event of selected cardiac cycles on a periodic basis.Offset interval generator produces an offset interval starting with thedetected timing reference event. The pulse delivery controller sends thepulse delivery signal to start a delivery of a burst of a plurality ofneural stimulation pulses when the offset interval expires. In oneembodiment, the pulse delivery controller sends the pulse deliverysignal after the detection of the timing reference event for each ofconsecutive cardiac cycles. In another embodiment, the pulse deliverycontroller sends the pulse delivery signal after the detection of thetiming reference event for selected cardiac cycles according to apredetermined pattern or schedule, such as on a periodic basis.

The data sensor 723A is used to detect a physiological response to theneural stimulation. In various embodiments, the data sensor 723A isadapted to detect a cardiac response or a non-cardiac response. Examplesof cardiac sensors include sensors to sense or detect HRV, HRT, PRinterval, T-wave velocity, and action potential duration. Examples ofnon-cardiac sensors include respiration sensors and blood pressuresensors. A feedback detection circuit 727 is connected to the datasensor to generate a feedback signal based on the sensed data. Forexample, one embodiment senses an ECG, and extracts a P-wave based onthe ECG signal. The therapy titration/adjustment circuit 730 in thestimulation control circuit is responsive to the feedback signal toadjust the therapy (e.g. change signal features, or change stimulationtargets, or change stimulation vectors). Contextual sensor(s) orinput(s) 723B are also illustrated connected to the feedback detectioncircuit 727. The feedback detection circuit can provide the neuralstimulation feedback signal based on the sensor 723A and the contextualinput(s) 723B. Examples of contextual inputs include an activity sensor,a posture sensor and a timer.

FIG. 8 is a block diagram illustrating an embodiment of a neuralstimulation system 821, which uses a wireless ECG to synchronize neuralstimulation to cardiac cycles. System 821 includes ECG electrodes 841,stimulation electrode/transducer 824 and a neural stimulation circuit818. Neural stimulation circuit 818 includes stimulation output circuit825, a cardiac event detection circuit 826, an arrhythmia detectioncircuit 842, a cardiac parameter measurement circuit 843, a cardiacfeedback detection circuit 827 and a stimulation control circuit 828.Contextual input(s) 823B are also illustrated connected to the feedbackdetection circuit 827.

In one embodiment, ECG electrodes 841 include surface ECG electrodes. Inanother embodiment, ECG electrodes 841 include electrodes for sensing awireless ECG signal. In one embodiment, ECG electrodes 841 includesubcutaneous electrodes for sensing a subcutaneous ECG signal. In oneembodiment, the subcutaneous electrodes are incorporated onto animplantable medical device, which is to be subcutaneously implanted. Inone embodiment, at least one subcutaneous electrode is placed in aselected location in the body near the base of the heart to allowselective detection of atrial depolarizations (P-waves). In anembodiment, multiple subcutaneous electrodes are placed near base andapex of the heart to allow P-wave detection by subtracting out unwantedactivities including ventricular depolarizations (R-waves). Thisapproach applies when it is difficult to isolate P-waves by selectingelectrode sites and filtering. At least one subcutaneous electrode isplaced near the apex of the heart to allow detection of R-waves. Thedetected R-waves are then used to isolate, by subtraction, P-waves froma subcutaneous ECG signal that includes both P-waves and R-waves.

The signal processor includes a wireless ECG sensing circuit to amplifyand filter the subcutaneous ECG signal sensed through ECG electrodes841. An example of electrodes and a circuit for sensing wireless ECGsignals including subcutaneous ECG signals is discussed in U.S. patentapplication Ser. No. 10/795,126, entitled “WIRELESS ECG IN IMPLANTABLEDEVICES,” filed on Mar. 5, 2004, assigned to Cardiac Pacemakers, Inc.,now U.S. Pat. No. 7,299,086, which is incorporated herein by referencein its entirety. In one embodiment, the timing reference event is aP-wave, such that cardiac event detection circuit 826 includes a P-wavedetector 844 to detect P-waves from the wireless ECG signal. In onespecific embodiment, P-wave detector 844 includes a filter having apass-band corresponding to a frequency range of P-waves. In anembodiment, P-wave detector 844 includes an R-wave detector to detectR-waves from one subcutaneous signal and a blanking period generator togenerate blanking periods to blank unwanted activities including theR-waves in another wireless ECG signal. In another specific embodiment,P-wave detector 844 includes an R-wave detector to detect R-waves fromthe subcutaneous signal and a timing interval generator to generate atiming interval upon detection of each R-wave. A P-wave is estimated tooccur at the end of the timing interval. The illustrated cardiacfeedback detection circuit 827 includes ECG parameter detectors such asheart rate detector 845 or other ECG parameter detector 846, which isused to provide a feedback signal to the stimulation control circuit.Arrhythmia detection circuit 842 and cardiac parameter measurementcircuit 843 provide for other control of neural stimulation based oncardiac conditions. Arrhythmia detection circuit 842 detects one or moretypes of arrhythmia from the wireless ECG signal. Cardiac parametermeasurement module 843 measures one or more cardiac parameters such as aheart rate and an atrioventricular interval from the wireless ECGsignal. Neural stimulation may be terminated or enabled, for example,using signals from the arrhythmia detection circuit and the cardiacparameter measurement module.

The illustrated stimulation control circuit 828 includes asynchronization module 829 and a therapy titration/adjustment module830. Synchronization module 829 synchronizes the delivery of the neuralstimulation pulses to the detected cardiac events such as P-waves. Inone embodiment, stimulation control circuit 828 includes an offsetinterval generator and pulse delivery controller. Synchronizationcircuit 829 can include one or both of a continuous synchronizationmodule to synchronize the delivery of the neural stimulation pulses tothe P-wave of each of consecutive cardiac cycles and a periodicsynchronization module to synchronize the delivery of the neuralstimulation pulses to the P-wave of each of selected cardiac cycles on aperiodic basis. The offset interval generator produces an offsetinterval starting with each detected P-wave. The pulse deliverycontroller sends the pulse delivery signal to start a delivery of aburst of a plurality of neural stimulation pulses when the offsetinterval expires. In an embodiment, the pulse delivery controller sendsthe pulse delivery signal after the detection of the P-wave for each ofconsecutive cardiac cycles. In an embodiment, the pulse deliverycontroller sends the pulse delivery signal after the detection of theP-wave for each of selected cardiac cycles according to a predeterminedpattern or schedule, such as on a periodic basis. The therapy titrationmodule 830 adjusts the therapy to achieve the desired cardiac activity(e.g. heart rate).

In an embodiment, stimulation control circuit 828 also controls thedelivery of the neural stimulation pulses based on the cardiac rhythmdetected by arrhythmia detection circuit 842 and/or the cardiacparameters measured by cardiac parameter measurement circuit 843. In oneembodiment, stimulation control circuit 828 withholds or adjusts thedelivery of the neural stimulation pulses when an arrhythmia isdetected. In another embodiment, stimulation control circuit 828 starts,stops, or adjusts the delivery of the neural stimulation pulses based onthe measured cardiac parameter, such as the heart rate and theatrioventricular interval.

FIG. 9 is an illustration of an embodiment of an electrode system forsensing one or more subcutaneous ECG signals. An electrode system forsubcutaneous ECG sensing includes two or more implantable electrodes.These implantable electrodes can be selected from the electrodesincluding, but not being limited to, those illustrated in FIG. 9. Theelectrodes are selected to allow for sensing electrical activities froma substantial portion of the heart, up to the entire heart. FIG. 9 showsan implantable medical device 947 and electrodes incorporated onto thatdevice. Implantable medical device 947 is to be subcutaneously implantedin a patient in need of neural stimulation to modulate cardiacfunctions. In an embodiment, one or more of the illustrated electrodesfunction as ECG electrodes. In another embodiment, in addition to one ormore electrodes shown in FIG. 9, ECG electrodes include one or moreelectrodes electrically connected to implantable medical device 947through a lead or a satellite wirelessly connected to an IMD.

Implantable medical device 947 includes a hermetically sealed can 948 tohouse its circuit. Can 948 has an outer surface subject to contact withbody tissue. Can 948 includes or provides for a base of a can electrode949 that is selectable as one of the electrodes for sensing asubcutaneous ECG signal. At least a portion of the outer surface of can948 is made of electrically conductive material. In one embodiment, can948 is used as can electrode 949. In an embodiment, can electrode 949includes at least one conductive portion of can 948. In an embodiment,can electrode 949 is incorporated onto the outer surface of can 948 andis electrically insulated from any conductive portion of can 948 using anon-conductive layer. In an embodiment, a hermetically sealedfeedthrough including a conductor provides for an electrical connectionbetween can electrode 949 and the circuit housed in can 948.

A header 950 is attached to can 948 and includes connectors providingfor electrical access to the circuit housed in can 948. In oneembodiment, one or more of header electrodes 951A-B are incorporatedinto the header. Header electrodes 951A-B are each selectable as one ofthe electrodes for sensing a subcutaneous ECG signal.

In one embodiment, two or more concentric electrodes 952A-C areincorporated onto the outer surface of can 948. Each of the concentricelectrodes 952A-C is selectable as one of the electrodes for sensing asubcutaneous ECG signal. Concentric electrodes 952A-C are insulated fromthe conductive portion of can 948 with a non-conductive layer andconnected to the circuit housed in can 948 via hermetically sealedfeedthroughs. In one embodiment, two electrodes, including an innerelectrode and an outer electrode, are selected from concentricelectrodes 952A-C for the wireless ECG sensing. In one embodiment, theouter electrode has a ring shape. In an embodiment, the outer electrodehas a shape approaching the contour of can 948.

In one embodiment, implantable medical device 947 includes an antenna953 used for a far-field RF telemetry link providing for communicationbetween implantable medical device 947 and an external system. Antenna953 is electrically connected to the circuit housed in can 948. In oneembodiment, antenna 953 projects from header 950 and extends along oneside of can 948. In one embodiment, antenna 953 includes a metalconductor with a distal portion exposed for functioning as an antennaelectrode 954, which is selectable as one of the electrodes for sensinga subcutaneous ECG signal.

The electrodes illustrated in FIG. 9 are intended to be examples but notlimitations. Other electrode configurations are usable as long as theysynchronize the delivery of neural stimulation pulses to cardiac cycles.In various embodiments in which multiple subcutaneous ECG vectors aresensed, multiple pairs of electrodes are selected, simultaneously or oneat a time, for a multi-channel (multi-vector) subcutaneous ECG sensing.In an embodiment, one or more of subcutaneous ECG vectors are sensed toapproximate one or more vectors of a standard multi-lead surface ECGrecording. In an embodiment, multiple subcutaneous ECG vectors aresensed based on needs of specific information for synchronizing thedelivery of neural stimulation pulses to cardiac cycles. Suchsubcutaneous ECG vectors do not necessarily approximate standard surfaceECG vectors. In an embodiment, implantable medical device 947 includesheader electrodes 951A-B and can electrode 949 for the subcutaneous ECGsensing. Implantable medical device 947 is programmable for sensingsubcutaneous ECG vectors between: header electrodes 951A and 951B;header electrode 951A and can electrode 949; and/or header electrode951B and can electrode 949. In an embodiment, implantable medical device947 includes one of header electrodes 951A-B, antenna electrode 954, andcan electrode 949 for the subcutaneous ECG sensing. Implantable medicaldevice 947 is programmable for sensing subcutaneous ECG vectors between:header electrode 951A or 951B and antenna electrode 954; headerelectrode 951A or 951B and can electrode 949; and/or antenna electrode954 and can electrode 949. In an embodiment, implantable medical device947 includes header electrodes 951A-B, antenna electrode 954, and canelectrode 949 for the subcutaneous ECG sensing. Implantable medicaldevice 947 is programmable for sensing subcutaneous ECG vectors between:header electrodes 951A and 954; header electrode 951A and antennaelectrode 954; header electrode 951A and can electrode 949; headerelectrode 951B and antenna electrode 954; header electrode 951B and canelectrode 949; and/or antenna electrode 954 and can electrode 949. Otherspecific embodiments involving any electrode combinations for thesubcutaneous ECG sensing will be employed based on needs andconsideration for synchronizing the delivery of neural stimulationpulses to cardiac cycles as well as needs and considerations forperforming other diagnostic and/or therapeutic functions provided byimplantable medical device 947.

The selection of subcutaneous ECG vectors depends on the purpose for thesubcutaneous ECG sensing. When the subcutaneous ECG signal is sensed fordetecting P-waves, the subcutaneous ECG vector that provide for areliable P wave detection are selected. When the subcutaneous ECG signalis sensed for detecting R-waves, one or more subcutaneous ECG vectorsthat provide for a reliable R wave detection are selected. In oneembodiment, when more than one subcutaneous ECG vector provides for areliable sensing for a particular purpose, the subcutaneous ECG vectorshowing the highest signal-to-noise ratio (SNR) for that purpose isselected. For example, if the subcutaneous ECG is sensed for detecting Pwaves, the subcutaneous ECG vector showing the highest SNR with P wavesbeing considered as the signal that is selected.

FIG. 10 is a block diagram illustrating an embodiment of a neuralstimulation system 1021 which uses heart sounds to synchronize neuralstimulation to cardiac cycles. System 1021 includes an acoustic sensor1022, a stimulation electrode or transducer 1024, and a neuralstimulation circuit 1018. Neural stimulation circuit 1018 includesstimulation output circuit 1025, a heart sound detection circuit 1026,feedback detection circuit 1027, and a stimulation control circuit 1028.Contextual sensor(s) or input(s) 1023B are also illustrated connected tothe feedback detection circuit 1027.

Acoustic sensor 1022 senses an acoustic signal indicative heart sounds.In one embodiment, acoustic sensor 1022 includes an implantable acousticsensor. In one embodiment, acoustic sensor 1022 includes anaccelerometer. In another embodiment, acoustic sensor 1022 includes amicrophone. In an embodiment, acoustic sensor 1022 is included in animplantable medical device. In an embodiment, acoustic sensor 1022 isincorporated onto a lead connected to an implantable medical device.

Heart sound detection circuit 1026 detects predetermined type heartsounds from the acoustic signal. Heart sound detection circuit 1026includes one or more of a first heart sound (S1) detector to detect S1,a second heart sound (S2) detector to detect S2, a third heart sound(S3) detector to detect S3, and a fourth heart sound (S4) detector todetect S4. In one embodiment, the type of heart sounds to be detected isdetermined based on whether each particular type of heart sounds isconsistently recurring and reliably detectable in an individual patient.In one embodiment, heart sound detection circuit 1026 includes a signalprocessor and an event detector. In an embodiment, heart sound detectioncircuit 1026 includes a filter having a pass-band corresponding to afrequency range of the predetermined type heart sounds. In anembodiment, heart sound detection circuit 1026 includes a signalaveraging circuit to average the acoustic signal over a predeterminednumber of cardiac cycles before the detection of the predetermined typeheart sounds. In an embodiment, heart sound detection circuit 1026receives an activity signal indicative of the patient's gross physicalactivity level and stops detecting heart sounds while the activitysignal exceeds a predetermined threshold activity level. In anembodiment, heart sound detection circuit 1026 includes an S2 detectorand/or an S3 detector such as those discussed in U.S. patent applicationSer. No. 10/746,853, “METHOD AND APPARATUS FOR THIRD HEART SOUNDDETECTION,” filed on Dec. 24, 2004, assigned to Cardiac Pacemakers,Inc., now U.S. Pat. No. 7,431,699, which is incorporated by reference inits entirety.

Stimulation control circuit 1028 includes a synchronization module 1029and a therapy titration/adjustment module 1030. Synchronization module1029 synchronizes the delivery of the neural stimulation pulses to thepredetermined type heart sounds. In one embodiment, stimulation controlcircuit 1028 includes an offset interval generator and pulse deliverycontroller. Synchronization circuit can include one or both of acontinuous synchronization module to synchronize the delivery of theneural stimulation pulses to the predetermined type heart sound of eachof consecutive cardiac cycles and a periodic synchronization module tosynchronize the delivery of the neural stimulation pulses to thepredetermined type heart sound of each of selected cardiac cycles on aperiodic basis. The offset interval generator produces an offsetinterval starting with the detected predetermined type heart sound. Thepulse delivery controller sends the pulse delivery signal to start adelivery of a burst of a plurality of neural stimulation pulses when theoffset interval expires. In one embodiment, the pulse deliverycontroller sends the pulse delivery signal after the detection of thepredetermined type heart sound for each of consecutive cardiac cycles.In an embodiment, the pulse delivery controller sends the pulse deliverysignal after the detection of the predetermined type heart sound foreach of selected cardiac cycles according to a predetermined pattern orschedule, such as on a periodic basis. The therapy titration module 1030receives a feedback signal from feedback detection circuit 1027. In theillustrated embodiment, the feedback detection circuit generates thefeedback signal using acoustic sensor 1022, although other sensed datacan be used to provide cardiac activity feedback.

FIG. 11 is a block diagram illustrating an embodiment of a neuralstimulation system 1121, which uses a hemodynamic signal to synchronizeneural stimulation to cardiac cycles. System 1121 includes a hemodynamicsensor 1122, a stimulation electrode or transducer 1124, and a neuralstimulation circuit 1118. Neural stimulation circuit 1118 includesstimulation output circuit 1125, a hemodynamic event detection circuit1126, a feedback detection circuit 1127, and a stimulation controlcircuit 1128. Contextual sensor(s) or input(s) 1123B are alsoillustrated connected to the feedback detection circuit 1127.

Hemodynamic sensor 1122 senses a hemodynamic signal indicative ofhemodynamic performance, such as a signal indicative of blood pressureor flow. In one embodiment, hemodynamic sensor 1122 is an implantablehemodynamic sensor. In one embodiment, hemodynamic sensor 1122 includesa Doppler echocardiographic transducer to sense a peripheral blood flow.In an embodiment, hemodynamic sensor 1122 includes a pressure sensor tosense a central or peripheral blood pressure. In an embodiment,hemodynamic sensor 1122 includes a pulse oximeter to sense an oximetrysignal, which is a plethysmographic signal indicative of blood flow. Inan embodiment, hemodynamic sensor 1122 includes a thoracic impedancesensor.

Hemodynamic event detection circuit 1126 detects predetermined typehemodynamic events from the hemodynamic signal. The hemodynamic eventscorrespond to a recurring feature of the cardiac cycle that is chosen tobe a timing reference to which the neural stimulation is synchronized.In one embodiment, hemodynamic event detection circuit 1126 includes apeak detector that detects predetermined type peaks in the hemodynamicsignal. In one embodiment, the peak detector is a pressure peak detectorthat detects predetermined type peaks in a blood pressure signal. In anembodiment, the peak detector includes a flow peak detector that detectspredetermined type peaks in a blood flow signal. The predetermined typepeaks are peaks indicative of a characteristic event that occurs duringeach cardiac cycle. In an embodiment, neural stimulation circuit 1118includes a derivative calculator to produce a derivative hemodynamicsignal by calculating a time derivative of the hemodynamic signal.Hemodynamic event detection circuit 1126 detects the predetermined typehemodynamic event from the derivative hemodynamic signal. In oneembodiment, the peak detector detects predetermined type peaks in thederivative hemodynamic signal. In one embodiment, the peak detector is apressure change peak detector that detects predetermined type peaks in aderivative hemodynamic signal indicative of changes in the bloodpressure (e.g., dP/dt). In an embodiment, the peak detector includes aflow change peak detector that detects predetermined type peaks in aderivative hemodynamic signal indicative changes in the blood flow.

The illustrated stimulation control circuit 1128 includes asynchronization module 1129 and a therapy titration module 1130.Synchronization module 1129 synchronizes the delivery of the neuralstimulation pulses to the predetermined type hemodynamic events. In oneembodiment, stimulation control circuit 1128 includes an offset intervalgenerator and pulse delivery controller. Synchronization circuit 1129includes one or both of a continuous synchronization module tosynchronize the delivery of the neural stimulation pulses to thepredetermined type hemodynamic event of each of consecutive cardiaccycles and a periodic synchronization module to synchronize the deliveryof the neural stimulation pulses to the predetermined type hemodynamicevent of each of selected cardiac cycles on a periodic basis. The offsetinterval generator produces an offset interval starting with eachdetected predetermined type hemodynamic event. The pulse deliverycontroller sends the pulse delivery signal to start a delivery of aburst of a plurality of neural stimulation pulses when the offsetinterval expires. In one embodiment, the pulse delivery controller sendsthe pulse delivery signal after the detection of the predetermined typehemodynamic event for each of consecutive cardiac cycles. In anembodiment, the pulse delivery controller sends the pulse deliverysignal after the detection of the predetermined type hemodynamic eventfor each of selected cardiac cycles according to a predetermined patternor schedule, such as on a periodic basis. The therapy titration module1130 receives a feedback signal from feedback detection circuit 1127. Inthe illustrated embodiment, the feedback detection circuit generates thefeedback signal using hemodynamic sensor 1122, although other senseddata can be used to provide cardiac activity feedback.

FIG. 12 illustrates an implantable medical device (IMD), according tovarious embodiments of the present subject matter. The illustrated IMD1253 provides neural stimulation signals for delivery to predeterminedneural targets. The illustrated device includes controller circuitry1254 and memory 1255. The controller circuitry is capable of beingimplemented using hardware, software, and combinations of hardware andsoftware. For example, according to various embodiments, the controllercircuitry includes a processor to perform instructions embedded in thememory to perform functions associated with the neural stimulationtherapy. The illustrated device further includes a transceiver 1256 andassociated circuitry for use to communicate with a programmer or anotherexternal or internal device. Various embodiments have wirelesscommunication capabilities. For example, some transceiver embodimentsuse a telemetry coil to wirelessly communicate with a programmer oranother external or internal device.

The illustrated device further includes neural stimulation outputcircuitry 1257 and sensor circuitry 1258. According to some embodiments,one or more leads are able to be connected to the sensor circuitry andneural stimulation circuitry. Some embodiments use wireless connectionsbetween the sensor(s) and sensor circuitry, and some embodiments usewireless connections between the stimulator circuitry and electrodes.According to various embodiments, the neural stimulation circuitry isused to apply electrical stimulation pulses to desired neural targets,such as through one or more stimulation electrodes 1259 positioned atpredetermined location(s). Some embodiments use transducers to provideother types of energy, such as ultrasound, light or magnetic energy. Invarious embodiments, the sensor circuitry is used to detectphysiological responses. Examples of physiological responses includecardiac activity such as heart rate, HRV, PR interval, T-wave velocity,and action potential duration. Other examples of physiological responsesinclude hemodynamic responses such as blood pressure, and respiratoryresponses such as tidal volume and minute ventilation. The controllercircuitry can control the therapy provided by system using a therapyschedule and a therapy titration routine in memory 1255, or can comparea target range (or ranges) of the sensed physiological response(s)stored in the memory 1255 to the sensed physiological response(s) toappropriately adjust the intensity of the neural stimulation/inhibition.

Some embodiments are adapted to change a stimulation signal feature, theneural stimulation target and/or change the neural stimulation vector aspart of a neural stimulation titration routine. According to variousembodiments using neural stimulation, the stimulation output circuitry1257 is adapted to set or adjust any one or any combination ofstimulation features based on commands from the controller 1254.Examples of stimulation features include the amplitude, frequency,polarity and wave morphology of the stimulation signal. Examples of wavemorphology include a square wave, triangle wave, sinusoidal wave, andwaves with desired harmonic components to mimic white noise such as isindicative of naturally-occurring baroreflex stimulation. Someembodiments are adapted to generate a stimulation signal with apredetermined amplitude, morphology, pulse width and polarity, and arefurther adapted to respond to a control signal from the controller tomodify at least one of the amplitude, wave morphology, pulse width andpolarity. Some embodiments are adapted to generate a stimulation signalwith a predetermined frequency, and are further adapted to respond to acontrol signal from the controller to modify the frequency of thestimulation signal.

The controller 1254 can be programmed to control the neural stimulationdelivered by the stimulation output circuitry 1257 according tostimulation instructions, such as a stimulation schedule, stored in thememory 1255. Neural stimulation can be delivered in a stimulation burst,which is a train of stimulation pulses at a predetermined frequency.Stimulation bursts can be characterized by burst durations and burstintervals. A burst duration is the length of time that a burst lasts. Aburst interval can be identified by the time between the start ofsuccessive bursts. A programmed pattern of bursts can include anycombination of burst durations and burst intervals. A simple burstpattern with one burst duration and burst interval can continueperiodically for a programmed period or can follow a more complicatedschedule. The programmed pattern of bursts can be more complicated,composed of multiple burst durations and burst interval sequences. Theprogrammed pattern of bursts can be characterized by a duty cycle, whichrefers to a repeating cycle of neural stimulation ON for a fixed timeand neural stimulation OFF for a fixed time.

According to some embodiments, the controller 1254 controls the neuralstimulation generated by the stimulation circuitry by initiating eachpulse of the stimulation signal. In some embodiments, the controllercircuitry initiates a stimulation signal pulse train, where thestimulation signal responds to a command from the controller circuitryby generating a train of pulses at a predetermined frequency and burstduration. The predetermined frequency and burst duration of the pulsetrain can be programmable. The pattern of pulses in the pulse train canbe a simple burst pattern with one burst duration and burst interval orcan follow a more complicated burst pattern with multiple burstdurations and burst intervals. In some embodiments, the controller 1254controls the stimulator output circuitry 1257 to initiate a neuralstimulation session and to terminate the neural stimulation session. Theburst duration of the neural stimulation session under the control ofthe controller 1254 can be programmable. The controller may alsoterminate a neural stimulation session in response to an interruptsignal, such as may be generated by one or more sensed parameters or anyother condition where it is determined to be desirable to stop neuralstimulation.

The sensor circuitry is used to detect a physiological response. Thedetected response can be cardiac activity or surrogates of cardiacactivity such as blood pressure and respiration measurements. Examplesof cardiac activity include a P-wave and heart rate. The controller 1254compares the response to a target range stored in memory, and controlsthe neural stimulation based on the comparison in an attempt to keep theresponse within the target range. The target range can be programmable.

The illustrated device includes a clock or timer 1260 which can be usedto execute the programmable stimulation schedule. For example, aphysician can program a daily schedule of therapy based on the time ofday. The therapy can be delivered in synchrony with cardiac activity(synch routine in memory 1255) and with cardiac activity feedback(titrate/feedback routine in memory 1255). A stimulation session canbegin at a first programmed time, and can end at a second programmedtime. Various embodiments initiate and/or terminate a stimulationsession based on a signal triggered by a user. Various embodiments usesensed data to enable and/or disable a stimulation session.

The illustrated memory includes a schedule. According to variousembodiments, the schedule refers to the time intervals or period whenthe neural stimulation therapy is delivered. A schedule can be definedby a start time and an end time, or a start time and a duration. Variousschedules deliver therapy periodically. According to various examples, adevice can be programmed with a therapy schedule to deliver therapy frommidnight to 2 AM every day, or to deliver therapy for one hour every sixhours, or to delivery therapy for two hours per day, or according to amore complicated timetable. Various device embodiments apply the therapyaccording to the programmed schedule contingent on enabling conditions,such as poor glucose control, patient rest or sleep, low heart ratelevels, and the like. The illustrated memory includes a synchronizationroutine and a titration feedback routine, which are used by the controlto control the timing and adjustments of neural stimulation generated bythe neural stimulator output circuitry.

FIG. 13 shows a system diagram of an embodiment of amicroprocessor-based implantable device, according to variousembodiments. The controller of the device is a microprocessor 1361 whichcommunicates with a memory 1362 via a bidirectional data bus. Thecontroller could be implemented by other types of logic circuitry (e.g.,discrete components or programmable logic arrays) using a state machinetype of design. As used herein, the term “circuitry” should be taken torefer to either discrete logic circuitry or to the programming of amicroprocessor. Shown in the figure are three examples of sensing andpacing channels designated “A” through “C” comprising bipolar leads withring electrodes 1363A-C and tip electrodes 1364A-C, sensing amplifiers1365A-C, pulse generators 1366A-C, and channel interfaces 1367A-C. Eachchannel thus includes a pacing channel made up of the pulse generatorconnected to the electrode and a sensing channel made up of the senseamplifier connected to the electrode. The channel interfaces communicatebidirectionally with the microprocessor, and each interface may includeanalog-to-digital converters for digitizing sensing signal inputs fromthe sensing amplifiers and registers that can be written to by themicroprocessor in order to output pacing pulses, change the pacing pulseamplitude, and adjust the gain and threshold values for the sensingamplifiers. The sensing circuitry of the pacemaker detects a chambersense, either an atrial sense or ventricular sense, when an electrogramsignal (i.e., a voltage sensed by an electrode representing cardiacelectrical activity) generated by a particular channel exceeds aspecified detection threshold. Pacing algorithms used in particularpacing modes employ such senses to trigger or inhibit pacing. Theintrinsic atrial and/or ventricular rates can be measured by measuringthe time intervals between atrial and ventricular senses, respectively,and used to detect atrial and ventricular tachyarrhythmias. The sensingof these channels can be used to detect cardiac activity for use insynchronizing neural stimulation and for use as feedback in titratingthe neural stimulation.

The electrodes of each bipolar lead are connected via conductors withinthe lead to a switching network 1368 controlled by the microprocessor.The switching network is used to switch the electrodes to the input of asense amplifier in order to detect intrinsic cardiac activity and to theoutput of a pulse generator in order to deliver a pacing pulse. Theswitching network also enables the device to sense or pace either in abipolar mode using both the ring and tip electrodes of a lead or in aunipolar mode using only one of the electrodes of the lead with thedevice housing (can) 1369 or an electrode on another lead serving as aground electrode. A shock pulse generator 1370 is also interfaced to thecontroller for delivering a defibrillation shock via a pair of shockelectrodes 1371 and 1372 to the atria or ventricles upon detection of ashockable tachyarrhythmia.

Neural stimulation channels, identified as channels D and E, areincorporated into the device for delivering parasympathetic stimulationand/or sympathetic inhibition, where one channel includes a bipolar leadwith a first electrode 1373D and a second electrode 1374D, a pulsegenerator 1375D, and a channel interface 1376D, and the other channelincludes a bipolar lead with a first electrode 1373E and a secondelectrode 1374E, a pulse generator 1375E, and a channel interface 1376E.Other embodiments may use unipolar leads in which case the neuralstimulation pulses are referenced to the can or another electrode. Thepulse generator for each channel outputs a train of neural stimulationpulses which may be varied by the controller as to amplitude, frequency,duty-cycle, and the like. In this embodiment, each of the neuralstimulation channels uses a lead which can be intravascularly disposednear an appropriate neural target. Other types of leads and/orelectrodes may also be employed. A nerve cuff electrode may be used inplace of an intravascularly disposed electrode to provide neuralstimulation. In some embodiments, the leads of the neural stimulationelectrodes are replaced by wireless links.

The figure illustrates a telemetry interface 1377 connected to themicroprocessor, which can be used to communicate with an externaldevice. The illustrated microprocessor is capable of performing neuralstimulation therapy routines and myocardial (CRM) stimulation routines.The neural stimulation routines can target nerves to affect cardiacactivity (e.g. heart rate and contractility). Examples of myocardialtherapy routines include bradycardia pacing therapies, anti-tachycardiashock therapies such as cardioversion or defibrillation therapies,anti-tachycardia pacing therapies (ATP), and cardiac resynchronizationtherapies (CRT).

FIG. 14 illustrates a system 1478 including an implantable medicaldevice (IMD) 1479 and an external system or device 1480, according tovarious embodiments of the present subject matter. Various embodimentsof the IMD include a combination of NS and CRM functions. The IMD mayalso deliver biological agents and pharmaceutical agents. The externalsystem and the IMD are capable of wirelessly communicating data andinstructions. In various embodiments, for example, the external systemand IMD use telemetry coils to wirelessly communicate data andinstructions. Thus, the programmer can be used to adjust the programmedtherapy provided by the IMD, and the IMD can report device data (such asbattery and lead resistance) and therapy data (such as sense andstimulation data) to the programmer using radio telemetry, for example.According to various embodiments, the IMD stimulates/inhibits a neuraltarget to affect cardiac activity.

The external system allows a user such as a physician or other caregiveror a patient to control the operation of the IMD and obtain informationacquired by the IMD. In one embodiment, external system includes aprogrammer communicating with the IMD bi-directionally via a telemetrylink. In another embodiment, the external system is a patient managementsystem including an external device communicating with a remote devicethrough a telecommunication network. The external device is within thevicinity of the IMD and communicates with the IMD bi-directionally via atelemetry link. The remote device allows the user to monitor and treat apatient from a distant location. The patient monitoring system isfurther discussed below.

The telemetry link provides for data transmission from implantablemedical device to external system. This includes, for example,transmitting real-time physiological data acquired by IMD, extractingphysiological data acquired by and stored in IMD, extracting therapyhistory data stored in implantable medical device, and extracting dataindicating an operational status of the IMD (e.g., battery status andlead impedance). Telemetry link also provides for data transmission fromexternal system to IMD. This includes, for example, programming the IMDto acquire physiological data, programming IMD to perform at least oneself-diagnostic test (such as for a device operational status), andprogramming the IMD to deliver at least one therapy.

FIG. 15 illustrates a system 1578 including an external device 1580, animplantable neural stimulator (NS) device 1581 and an implantablecardiac rhythm management (CRM) device 1582, according to variousembodiments of the present subject matter. Various aspects involve amethod for communicating between an NS device and a CRM device or othercardiac stimulator. In various embodiments, this communication allowsone of the devices 1581 or 1582 to deliver more appropriate therapy(i.e. more appropriate NS therapy or CRM therapy) based on data receivedfrom the other device. Some embodiments provide on-demandcommunications. In various embodiments, this communication allows eachof the devices to deliver more appropriate therapy (i.e. moreappropriate NS therapy and CRM therapy) based on data received from theother device. For example, ECG data from the CRM device can becommunicated to the NS device for use in synchronizing and titrating theneural stimulation. The illustrated NS device and the CRM device arecapable of wirelessly communicating with each other, and the externalsystem is capable of wirelessly communicating with at least one of theNS and the CRM devices. For example, various embodiments use telemetrycoils to wirelessly communicate data and instructions to each other. Inother embodiments, communication of data and/or energy is by ultrasonicmeans. Rather than providing wireless communication between the NS andCRM devices, various embodiments provide a communication cable or wire,such as an intravenously-fed lead, for use to communicate between the NSdevice and the CRM device. In some embodiments, the external systemfunctions as a communication bridge between the NS and CRM devices.

FIG. 16 is a block diagram illustrating an embodiment of an externalsystem 1680. The external system includes a programmer, in someembodiments. In the illustrated embodiment, the external system includesa patient management system. As illustrated, the external system 1680 isa patient management system including an external device 1683, atelecommunication network 1684, and a remote device 1685. Externaldevice 1683 is placed within the vicinity of an IMD and includesexternal telemetry system 1686 to communicate with the IMD. Remotedevice(s) 1685 is in one or more remote locations and communicates withexternal device 1683 through network 1684, thus allowing a physician orother caregiver to monitor and treat a patient from a distant locationand/or allowing access to various treatment resources from the one ormore remote locations. The illustrated remote device includes a userinterface 1687.

FIG. 17 illustrates a system embodiment in which an IMD 1788 is placedsubcutaneously or submuscularly in a patient's chest with lead(s) 1789positioned to stimulate a vagus nerve. According to various embodiments,neural stimulation lead(s) 1789 are subcutaneously tunneled to a neuraltarget, and can have a nerve cuff electrode to stimulate the neuraltarget. Some vagus nerve stimulation lead embodiments areintravascularly fed into a vessel proximate to the neural target, anduse electrode(s) within the vessel to transvascularly stimulate theneural target. For example, some embodiments stimulate the vagus usingelectrode(s) positioned within the internal jugular vein. Otherembodiments deliver neural stimulation to the neural target from withinthe trachea, the laryngeal branches of the internal jugular vein, andthe subclavian vein. The neural targets can be stimulated using otherenergy waveforms, such as ultrasound and light energy waveforms. Otherneural targets can be stimulated, such as cardiac nerves and cardiac fatpads. The illustrated system includes leadless ECG electrodes on thehousing of the device. These ECG electrodes 1790 are capable of beingused to detect heart rate, for example. Various embodiments includelead(s) positioned to provide a CRM therapy to a heart, and with lead(s)positioned to stimulate and/or inhibit neural traffic at a neuraltarget, such as a vagus nerve, according to various embodiments.

FIG. 18 illustrates a system embodiment that includes an implantablemedical device (IMD) 1888 with satellite electrode(s) 1889 positioned tostimulate at least one neural target. The satellite electrode(s) areconnected to the IMD, which functions as the planet for the satellites,via a wireless link. Stimulation and communication can be performedthrough the wireless link. Examples of wireless links include RF linksand ultrasound links. Examples of satellite electrodes includesubcutaneous electrodes, nerve cuff electrodes and intravascularelectrodes. Various embodiments include satellite neural stimulationtransducers used to generate neural stimulation waveforms such asultrasound and light waveforms. The illustrated system includes leadlessECG electrodes on the housing of the device. These ECG electrodes 1890are capable of being used to detect heart rate, for example. Variousembodiments include lead(s) positioned to provide a CRM therapy to aheart, and with satellite transducers positioned to stimulate/inhibit aneural target such as a vagus nerve, according to various embodiments.

One of ordinary skill in the art will understand that the modules andother circuitry shown and described herein can be implemented usingsoftware, hardware, and combinations of software and hardware. As such,the term module is intended to encompass software implementations,hardware implementations, and software and hardware implementations.

The methods illustrated in this disclosure are not intended to beexclusive of other methods within the scope of the present subjectmatter. Those of ordinary skill in the art will understand, upon readingand comprehending this disclosure, other methods within the scope of thepresent subject matter. The above-identified embodiments, and portionsof the illustrated embodiments, are not necessarily mutually exclusive.These embodiments, or portions there of, can be combined. In variousembodiments, the methods provided above are implemented as a computerdata signal embodied in a carrier wave or propagated signal, thatrepresents a sequence of instructions which, when executed by aprocessor cause the processor to perform the respective method. Invarious embodiments, methods provided above are implemented as a set ofinstructions contained on a computer-accessible medium capable ofdirecting a processor to perform the respective method. In variousembodiments, the medium is a magnetic medium, an electronic medium, oran optical medium.

Although specific embodiments have been illustrated and describedherein, it will be appreciated by those of ordinary skill in the artthat any arrangement which is calculated to achieve the same purpose maybe substituted for the specific embodiment shown. This application isintended to cover adaptations or variations of the present subjectmatter. It is to be understood that the above description is intended tobe illustrative, and not restrictive. Combinations of the aboveembodiments as well as combinations of portions of the above embodimentsin other embodiments will be apparent to those of skill in the art uponreviewing the above description. The scope of the present subject mattershould be determined with reference to the appended claims, along withthe full scope of equivalents to which such claims are entitled.

What is claimed is:
 1. A method for treating a patient, comprising:detecting an electric pulse generated by a cardiac rhythm management(CRM) device; and activating a baroreflex therapy in response to thedetected electric pulse, or if the baroreflex therapy is currentlyactivated increasing an intensity of the baroreflex activation therapyupon detection of the electric pulse.
 2. The method of claim 1, whereinthe CRM device comprises a pacemaker, a cardiac resynchronizationtherapy (CRT) device, or a cardioverter.
 3. The method of claim 1,further comprising discontinuing the activation of the baroreflex systemof the patient after expiration of a pre-selected period of time.
 4. Themethod of claim 1, wherein the baroreflex therapy is activated inresponse to the detected electric pulse.
 5. The method of claim 4,wherein the CRM device comprises a defibrillator.
 6. The method of claim4, further comprising discontinuing the activation of the baroreflexsystem of the patient after expiration of a pre-selected period of time.7. The method of claim 4, wherein the baroreflex system of the patientis activated after expiration of a pre-selected period of time.
 8. Themethod of claim 7, wherein the CRM device comprises a pacemaker.
 9. Themethod of claim 7, wherein the CRM device comprises a cardiacresynchronization therapy (CRT) device.
 10. The method of claim 7,wherein the CRM device comprises a cardioverter.
 11. The method of claim7, wherein detecting the electric pulse generated by the CRM devicecomprises measuring a voltage difference between a BAT electrode and ahousing of a BAT device.
 12. The method of claim 7, wherein detectingthe electric pulse generated by the CRM device comprises measuring avoltage difference between a lead of the CRM device and a housing of aBAT device.
 13. The method of claim 7, wherein detecting the electricpulse generated by the CRM device comprises measuring a voltagedifference between a lead of the CRM device and an electrode of a BATdevice.
 14. The method of claim 1, wherein the method includes:delivering baroreflex activation therapy to a body of the patient andincreasing an intensity of the baroreflex activation therapy upondetection of the electrical pulse.
 15. The method of claim 14, whereinthe CRM device comprises an implantable defibrillator.
 16. The method ofclaim 14, further comprising returning the baroreflex activation therapyto an original intensity after expiration of a pre-selected period oftime.
 17. The method of claim 1, wherein the method includes deliveringbaroreflex activation therapy to a body of the patient at a firstintensity and delivering baroreflex activation therapy to the body ofthe patient at a second intensity after the electrical pulse has beendetected.
 18. The method of claim 17, wherein the second intensity isgreater than the first intensity.
 19. The method of claim 17, whereinthe CRM device comprises an implantable defibrillator.
 20. The method ofclaim 17, further comprising delivering baroreflex activation therapy tothe body of the patient at the first intensity after expiration of apre-selected period of time.